Medical Genetics Institute, Meir Medical Center, Kfar Saba, Israel.
Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel.
Clin Genet. 2017 Dec;92(6):645-648. doi: 10.1111/cge.13020. Epub 2017 Aug 3.
Metaphyseal anadysplasia (MANDP) is a rare autosomal recessive form of skeletal dysplasia characterized by normal length at birth and transitory bowing of the legs. Although several families with MANDP have been reported, homozygous mutations in the matrix metalloproteinase type 9 (MMP9) gene have been described in only one consanguineous family, and thus the pre and postnatal phenotypic spectrum is still obscure. A clinically similar but more severe type is caused by autosomal-dominant inheritance and is caused by mutations in matrix metalloproteinase type 13 gene (MMP13). Here, we report the prenatal and early postnatal course of two affected sib fetuses with early sonographic evidence of long bone shortening and postnatally no metaphyseal changes. Whole-exome sequencing revealed homozygous mutation in MMP9 in both fetuses suggesting a diagnosis of MANDP. We propose that MANDP should be considered in pregnancies with early prenatal shortening of the long bones without associated finding of lethal skeletal dysplasias. In addition, the finding of homozygous mutation in non-consanguineous parents of Jewish-Caucasus ancestry may suggest unawareness of such relation or the occurrence of a founder mutation in this gene.
干骺端发育不良（MANDP）是一种罕见的常染色体隐性骨骼发育不良，其特征是出生时长度正常，腿部短暂弯曲。虽然已经报道了几个 MANDP 家族，但仅在一个近亲结婚的家庭中描述了基质金属蛋白酶 9 型（MMP9）基因突变的纯合子，因此产前和产后表型谱仍然不清楚。一种临床相似但更严重的类型是由常染色体显性遗传引起的，由基质金属蛋白酶 13 型基因（MMP13）的突变引起。在这里，我们报告了两例受影响的同胞胎儿的产前和早期产后病程，这些胎儿具有长骨缩短的早期超声证据，而产后没有干骺端变化。全外显子组测序显示这两个胎儿均存在 MMP9 纯合突变，提示诊断为 MANDP。我们建议，在没有致死性骨骼发育不良相关发现的情况下，对于产前长骨早期缩短的妊娠，应考虑 MANDP。此外，在犹太-高加索血统的非近亲父母中发现同源突变，可能表明他们不知道这种关系，或者该基因中发生了一个奠基突变。
